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Transduction motif analysis of gastric cancer based on a human signaling network

机译:基于人类信号网络的胃癌转导基序分析

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To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD) scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR,MAPK14, BCL2L1, KRT18,PTPN6, CASP3, TGFBR2,AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.
机译:为了研究胃癌的信号调节模型,数据库和文献被用来构建人类的信号网络。通过CytoScape分析了网络的拓扑特征。在标记从CancerResource,GeneRIF和COSMIC数据库中提取的胃癌相关基因后,将FANMOD软件用于在具有三个顶点的网络中挖掘胃癌相关基序。采用显着的基序差异方法来识别正常和癌症状态下的显着不同的基序。最后,我们对明显不同的基序进行了一系列分析,包括基因本体论,基因功能注释和模型分类。构建了一个人类信令网络,该网络具有1643个节点和5089个调节交互的对象。该网络配置为具有其他生物网络的特征。在总共69,492个基序中,有57,942个标有胃癌相关基因的基序,并且通过计算显着基序差异(SMD)得分,选择了264个基序作为显着不同的基序。具有显着不同基序的基因主要富含与癌症发生相关的功能,例如细胞死亡的调控,蛋白质的氨基酸磷酸化和细胞内信号传导级联。前五个明显不同的图案主要是层叠和正反馈类型。这五个基序中的几乎所有基因都与癌症相关,包括EPOR,MAPK14,BCL2L1,KRT18,PTPN6,CASP3,TGFBR2,AR和CASP7。可以通过抑制所选基序上游和下游的信号转导来抑制癌症的发展。

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